2-(allylthio)pyrazine and Disease-Models--Animal

The lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) in the vascular wall accounts, at least in part, for the severe hypotension in endotoxemia. The present study investigated whether 2-(allylthio)pyrazine (2-AP), an antioxidant, affects the LPS-induced expression of iNOS in rat aortic rings and the LPS-induced mortality in mice. 2-AP prevented the LPS-induced attenuation of contractions to phenylephrine, formation of cyclic GMP, and expression of iNOS in aortic rings without endothelium and caused endothelium-dependent nitric oxide-mediated relaxations. The mortality of mice receiving a lethal bolus of LPS was decreased by 2-AP, and this effect was associated with a reduced serum nitrite and nitrate level. These findings suggest that agents which inhibit the expression of iNOS but stimulate the formation of endothelium-derived nitric oxide may be of therapeutical value for the treatment of endotoxemia.

Topics: Animals; Cyclic GMP; Disease Models, Animal; Endothelium, Vascular; Endotoxemia; Enzyme Inhibitors; Lipopolysaccharides; Male; Mice; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Organ Culture Techniques; Phenylephrine; Pyrazines; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasoconstrictor Agents; Vasodilation